Saccharomyces cerevisiae DNA helicases Mph1, Srs2 and Sgs1 collaborate for the reinitiation of stalled or collapsed replication forks

Abstract

Exogenous agents such as UV light and ionizing radiation or endogenous agents such as water and reactive oxygen species, generated during respiration, are responsible for the generation of DNA damages. They are mainly represented by strand breaks, base modification and bulky adducts (Oakley and Hickson 2002) and they may provoke the arrest of replication forks since the tight binding pocket of the replicative polymerases prevents the copying of damaged nucleotides in the template strand (Friedberg et al 2001;Kool et al 2002). Furthermore, secondary lesions such as DNA double strand ends may arise when the replication fork runs into unrepaired nicks or gaps in the template strand thus causing fork collapse (Kuzminov 1995). Sensors Rad24 RAD17 RCF like lamp loader Ddc1 RAD9 PCNA like clamp Mec3 HUS1 PCNA like clamp Rad17 RAD1 PCNA like clamp Mec1 ATR PI3 like kinase Dcd2/Pie1/Lcd1 ATRIP Interaction with Mec1 and ATR Tel1 ATM PI3 like kinase Mediators Rad9 BRCA1 Mediates activation of effectors Mrc1 Claspin Mediates activation of effectors Effectors Rad53 CHK2 S/T kinase Chk1 CHK1 KinaseIt is suggested that the DNA damage checkpoint response during replication is triggered through the recognition of DNA abnormalities common to all DNA lesions.